Hydrophobicity of Di‐ and Tripeptides Having Unionizable Side Chains and Correlation with Substituent and Structural Parameters

Akamatsu, Miki; Yoshida, Yohji; Nakamura, Hideaki; Asao, Masaaki; Iwamura, Hajime; Fujita, Toshio

doi:10.1002/qsar.19890080302

Cited by 56 publications

(42 citation statements)

References 27 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of a zwitterionic buffer avoids the formation of ion pairs with ionized peptides, which would partition into the org. phase [6]. The speed of rotation was set at 1000 rpm and the applied flow rate between 0.3 and 6.5 ml/min.…”

Section: Measurement Of Distribution Coefficients (Log D Values) Octmentioning

confidence: 99%

See 1 more Smart Citation

Structure‐Lipophilicity and Structure‐Polarity relationships of amino acids and peptides

Vallat

Gaillard

Carrupt

et al. 1995

Helvetica Chimica Acta

View full text Add to dashboard Cite

(3 1. X. 94) The objectives of this study were to gain insights into the structure-lipophilicity relationships of peptides and to propose an improved model for estimating their lipophilicity. First, existing databases were extended to obtain the distribution coefficients of a total of 208 free or protected peptides (di-to pentapeptides). The polarity parameters ( A j of 23 free amino acids and 19 protected amino acids (AcNH-CHR-CONH,) and of their side chains were Calculated from experimental distribution coefficients and computed molecular volumes. An analysis of the polarity parameters revealed that the hydrophobicity of the amino-acid side chains is largely reduced due to the polar field of the backbone. The polarity parameters of the peptides were then obtained in a similar manner and shown to be highly correlated with the sum of the polarity parameters of their side chains, i.e., the lipophilicity of peptides can be calculated from their molecular volume and the sum of their side-chain polarities using the regression established for each individual series of peptides (Fig. I). This last restriction is essential since the polarity and lipophilic increment of a NH-C*H-CO unit were shown to decrease with increasing length of backbone. Introduction.-Endogenous peptides such as many hormones and neurotransmitters were found to modulate a wide variety of biological functions [ 11 121. The potency and specificity of these endogenous compounds make it clear why the design of synthetic peptides and of peptidomimetics is already one of the major issues in drug research. Indeed, these approaches led to the discovery of new lead compounds and drugs such as potent peptide receptor antagonists and enzyme inhibitors.Peptides and their constituent amino acids show a wide range of physicochemical and structural properties. Amino-acid side chains contain polar, non-polar, charged, or uncharged groups and differ considerably in size and flexibility. Characterizing the structural and physicochemical properties of amino acids and peptides is an important condition in molecular biology to unravel the properties of proteins, and in molecular pharmacology to rationalize and predict the biological properties of peptide drugs. What is at stake here is a better understanding of structure-property-activity relationships of peptides. In this context, lipophilicity parametrization of amino acids and peptides is of major concern. Indeed, lipophilicity is a physicochemical property of particular significance in drug design, because it encodes a wealth of information on a solute's structure and the intermolecular interactions it elicits [3-51.Lipophilicity can be expressed by the logarithm of the partition coefficient (i.e. log P, which refers to a well-defined electrical state of the solute, for example the neutral or

show abstract

Section: Measurement Of Distribution Coefficients (Log D Values) Octmentioning

confidence: 99%

“…The studies of Akamatsu et al [6] [8] contain 32 free dipeptides and 38 free tripeptides. We extended this database by measuring the log D values at pH 7.0 of 11 free dipeptides and 10 free tripeptides using centrifugal partition chromatography.…”

mentioning

confidence: 99%

Structure‐Lipophilicity and Structure‐Polarity relationships of amino acids and peptides

Vallat

Gaillard

Carrupt

et al. 1995

Helvetica Chimica Acta

View full text Add to dashboard Cite

show abstract

“…The sequences and the logP value of the studied peptides were collected from the literature [1][2][3][4][5], which can be seen in Table 4. …”

Section: Logp For Unblocked Dipeptidesmentioning

confidence: 99%

“…Therefore, it is important meaningful to study the relationships between peptide logP and its structure by theory tool both in academic significance and application value. The literatures [1][2][3][4][5] built a linear model for calculation of logP by the hydrophobic parameter  and index variable of amino acids. Tao Peng et al [6] had been constructed the multivariate linear regression logP prediction model of peptides using the contribution addition method of amino acid side chain.…”

Section: Introductionmentioning

confidence: 99%

A Simple, Yet Rapid and Effective Method for LogP Prediction of Dipeptides Based on Theoretical Descriptors (HMLP)

Yin¹,

Liu²

2011

IJEM

View full text Add to dashboard Cite

The hydrophobicity of peptide is an important factor that affects the dissolution behavior of proteins and peptides, also affect the physical and chemical properties. In this study, each amino acid side chain was characterized using three structure parameters (heuristic molecular lipophilicity potential, HMLP). The HMLP parameters, total surface area(S), lipophilic indices (L), and hydrophilic indices (H) of amino acid side chains are derived from theoretical computation. Based on HMLP descriptors, QSAR models of the logP were constructed for blocked and unblocked dipeptides by multiple linear regression (MLR) and support vector regression (SVR). All the results showed that the logP relates to the total surface area(S) and hydrophilic indices (H), and the prediction results of SVR are better than that of MLR. The prediction results are in agreement with the experimental values. The result shows HMLP parameters (S,L,H) could preferably describe the structure features of the peptides responsible for their octanol to water partition behavior.

show abstract

“…The very recent interest of medicinal chemists for peptides explains the poor number of studies reported in the literature so far to predict their lipophilicity [9][10][11][12]. Nowadays, peptide lipophilicity prediction is mostly performed by using algorithms developed for organic molecules.…”

Section: Introductionmentioning

confidence: 99%

Prediction and interpretation of the lipophilicity of small peptides

Visconti

Ermondi

Esposito

2015

J Comput Aided Mol Des

View full text Add to dashboard Cite

Peptide-based drug discovery has considerably expanded and solid in silico tools for the prediction of physico-chemical properties of peptides are urgently needed. In this work we tested some combinations of descriptors/algorithms to find the best model to predict log D oct of a series of peptides. To do that we evaluate the models statistical performances but also their skills in providing a reliable deconvolution of the balance of intermolecular forces governing the partitioning phenomenon. Results prove that a PLS model based on VolSurf+ descriptors is the best tool to predict log D oct of neutral and ionised peptides. The mechanistic interpretation also reveals that the inclusion in the chemical structure of a HBD group is more efficient in decreasing lipophilicity than the inclusion of a HBA group.

show abstract

Hydrophobicity of Di‐ and Tripeptides Having Unionizable Side Chains and Correlation with Substituent and Structural Parameters

Cited by 56 publications

References 27 publications

Structure‐Lipophilicity and Structure‐Polarity relationships of amino acids and peptides

Structure‐Lipophilicity and Structure‐Polarity relationships of amino acids and peptides

A Simple, Yet Rapid and Effective Method for LogP Prediction of Dipeptides Based on Theoretical Descriptors (HMLP)

Prediction and interpretation of the lipophilicity of small peptides

Contact Info

Product

Resources

About